Main group boryl compounds have found many industrial applications, for example in the pharmaceutical and agricultural industries, as well as in specialty and solid state chemical fields. Main group boryl compounds are also remarkably useful synthetic intermediates.
Compounds containing boronic acids (RB(OH)2) or boronate esters (RB(OR′)2) have received considerable attention in catalysed carbon-carbon bond formation reactions [(a) N. Miyaura and A. Suzuki, Chem. Rev. 1995, 95, 2457. (b) B. M. Trost and M. D. Spagnol, J. Chem. Soc., Perkin Trans 1 1995, 2083. (c) D. M. T. Chan, K. L. Monaco, R. P. Wang and M. P. Winters, Tetrahedron Lett. 1998, 39, 2933. (d) F. Berrée, P. Girard-Le Bleis and B. Carboni, Tetrahedron Lett. 2002, 43, 4935. (e) S. Sakuma and N. Miyaura, J. Org. Chem. 2001, 66, 8944.], solid-phase synthesis (B. Carboni, C. Pourbaix, F. Carreaux, H. Deleuze and B. Maillard, Tetrahedron Lett. 1999, 40, 7979.), macrocyclic chemistry (N. Farfan, H. Hopfl, V. Barba, M. E. Ochoa, R. Santillan, E. Gomez and A. Gutierrez, J. Organomet. Chem. 1999, 581, 70.), organometallic and organic synthesis [(a) F. Minutolo and J. A. Katzenellenbogen, Organometallics 1999, 18, 2519. (b) D. S. Matteson, Tetrahedreon 1989, 45, 1859. (c) J. Tailor and D. G. Hall, Org. Lett. 2000, 2, 3715. (d) N. A. Petasis and I. A. Zavialov, J. Am. Chem. Soc. 1998, 120, 11798. (e) R. A. Batey, D. B. MacKay and V. Santhakumar, J. Am. Chem. Soc. 1999, 121, 5075.] and as glucose sensors for diabetes therapy [(a) M. Yamamoto, M. Takeuchi and S. Shinkai, Tetrahdedron, 1998, 54, 3125. (b) H. Eggert, J. Frederiksen, C. Morin and J. Chr. Norrild, J. Org. Chem. 1999, 64, 3846. (c) S. Arimori, C. J. Ward and T. D. James, Tetrahedron Lett. 2002, 43, 303. (d) W. Wang, X. Gao and B. Wang, Curr. Org. Chem. 2002, 6, 1285.]. Over the years, interest in compounds containing boronic acids or boronate esters have also arisen because of the potent biological activities of these compounds [(a) T. D. James, P. Linnane and S. Shinkai, J. Chem. Soc., Chem. Commun. 1996, 281. (b) W. Yang, X. Gao and B. Wang, Med. Res. Rev. 2003, 23, 346. (c) C. Morin, Tetrahedron 1994, 50, 12521. (d) V. S. Stoll, B. T. Eger, R. C. Hynes, V. Martichonok, J. B. Jones and E. F. Pai, Biochemistry 1998, 37, 451. (e) S. J. Coutts, T. A. Kelly, R. J. Snow, C. A. Kennedy, R. W. Barton, J. Adams, D. A. Krolikowski, D. M. Freeman, S. J. Campbell, J. F. Ksiazek and W. W. Bachovchin, J. Med. Chem. 1996, 39, 2087. (f) E. S. Priestley and C. P. Decicco, Org. Lett. 2000, 2, 3095. (g) E. Skordalakes, R. Tyrell, S. Elgendy, C. A. Goodwin, D. Green, G. Dodson, M. F. Scully, J. M. H. Freyssinet, V. V. Kakkar and J. J. Deadman, J. Am. Chem. Soc. 1997, 119, 9935. (h) M. L. Stolowitz, C. Ahlem, K. A. Hughes, R. J. Kaiser, E. A. Kesicki, G. Li, K. P. Lund, S. M. Torkelson and J. P. Wiley, Bioconjugate Chem. 2001, 12, 229. (i) S. Jagannathan, T. P. Forsyth and C. A. Kettner, J. Org. Chem. 2001, 66, 6375. (j) R. C. Gardner, S. J. Assinder, G. Christie, G. G. F. Mason, R. Markwell, H. Wadsworth, M. Mclaughlin, R. King, M. C. Chabot-Fletcher, J. J. Breton, D. Allsop and A. J. Rivett, Biochem. J. 2000, 346, 447. (k) S. Collet, F. Carreaux, J. L. Boucher, S. Pethe, M. Lepoivre, R. Danion-Bougot and D. Danion, J. Chem. Soc., Perkin Trans. 1 2000, 177. (l) P. Mantri, D. E. Duffy and C. A. Kettner, J. Org. Chem. 1996, 61, 5690. (m) J. Lin and B. R. Shaw, Chem. Commun. 1999, 1517. (n) B. K. Shull, D. E. Spielvogel, R. Gopalaswamy, S. Sankar, P. D. Boyle, G. Head and K. Devito, J. Chem. Soc., Perkin Trans. 2 2000, 557. (o) I. Pergament and M. Srebnik, Tetrahedron Lett. 1999, 40, 3895. (p) P. R. Westmark and B. D. Smith, J. Am. Chem. Soc. 1994, 116, 9343.].
As an example, α-aminoboronic acids having the general formula of:
are effective and reversible inhibitors of serine proteases—a diverse group of proteoloytic enzymes whose numerous physiological functions include digestion, growth, differentiation and apoptosis. Since proteases have also been found to be vital in the generation of most disease processes, much effort has been focused on the synthesis of α-aminoboronic acids for possible applications as enzyme inhibitors.
Amino acid analogs containing boronic acids have been investigated for their use in boron neutron capture therapy (BNCT) for the treatment of cancer [(a) L. Weissfloch, M. Wagner, T. Probst, R. Senekowitsch-Schmidtke, K. Tempel and M. Molls, Biometals 2001, 14, 43. (b) J. Thomas and M. F. Hawthorne, Chem. Commun. 2001, 1884. (c) I. B. Sivaev, A. B. Bruskin, V. V. Nesterov, M. Y. Antipin, V. I. Bregadze and S. Sjöberg, Inorg. Chem. 1999, 38, 5887. (d) E. B. Kullberg, N. Bergstrand, J. Carlsson, K. Edwards, M. Johnsson, S. Sjöberg and L. Gedda, Bioconjugate Chem. 2002, 13, 737. (e) R. R. Srivastava and G. W. Kabalka, J. Org. Chem. 1997, 62, 8730. (f) G. W. Kabalka, B. C. Das and S. Das, Tetrahedron Lett. 2001, 42, 7145. (g) X. Q. Pan, H. Wang, S. Shukla, M. Sekido, D. M. Adams, W. Tjarks, R. F. Barth and R. L. Lee, Bioconjugate Chem. 2002, 13, 435. (h) J. Cai, A. H. Soloway, R. F. Barth, D. M. Adams, J. R. Hariharan, I. M. Wyzlic and K. Radcliffe, J. Med. Chem. 1997, 40, 3887. (i) J. C. Zhuo, J. Cai, A. H. Soloway, R. F. Barth, D. M. Adams, W. Ji and W. Tjarks, J. Med. Chem. 1999, 42, 1282. (j) A. H. Soloway, W. Tjarks, B. A. Barnum, F. G. Rong, R. F. Barth, I. M. Codogni and J. G. Wilson, Chem. Rev. 1998, 98, 1515.] BNCT is a bimodal form of therapy which depends on selectively depositing boron-10 atoms into the cancerous tumour prior to irradiation by slow (thermal) neutrons.
An example of an amino acid analog containing boronic acid is 4-dihydroxyborylphenylalanine (BPA):
which is a simple second generation BNCT compound, potentially useful in the treatment of brain tumours (A. H. Soloway, W. Tjarks, B. A. Barnum, F. G. Rong, R. F. Barth, I. M. Codogni and J. G. Wilson, Chem. Rev. 1998, 98, 1515.).
Furthermore, recent work has found that certain boron compounds also show considerable antifungal (C. M. Vogels, L. G. Nilolcheva, H. A. Spinney, D. W. Norman, M. O. Baerlocher, F. J. Baerlocher and S. A. Westcott, Can. J. Chem. 2001, 79, 1115) and antibacterial activity (S. Gronowitz, T. Dalgren, J. Namtvedt, C. Roos, B. Sjöberg and U. Forsgren, Acta Pharm. Suecica, 1971, 8, 377). Indeed, the compound 2-formylphenylboronic acid:
is a strong fungicidal agent against both Aspergillus niger and Aspergillus flavus. 
Silylboryl compounds of the general formula [R3SiB(XR′)2] have also been of special interest because of their properties [(a) M. Suginome and Y. Ito, J. Organomet Chem. 2003, 680, 43. (b) J. C. A. Da Silva, M. Birot, J. P. Pillot and M. Pétraud, J. Organomet. Chem. 2002, 646, 179. (c) T. Kajiwara, N. Takeda, T. Sasamori and N. Tokitoh, Organometallics, 2004, 23, 4723.] A comprehensive review on the chemistry of silylboranes has recently been published (M. Suginome and Y. Ito, J. Organomet. Chem. 2003, 680, 43). However, despite many of the interesting properties and applications associated with silylboranes, their chemistry has not yet been fully explored, mainly due to the limited synthetic methods for the preparation of these remarkable compounds.
Traditional routes to organoborate esters are based on the alkylation of trialkylborates with organomagnesium or organolithium reagents (A. Pelter, K. Smith and H. C. Brown, Borane Reagents, Academic Press, London, 1998). However, these reactions usually suffer from low yields. Further, the reactions are often complicated by the formation of a mixture of either magnesium or lithium salts.
The uncatalyzed addition of hydroboranes to unsaturated hydrocarbons presents another route to organoborate esters. However, this reaction suffers from selectivity problems.
New methodologies to solve the difficulties associated with making these valuable boryl compounds will no doubt have a tremendous impact in organic synthesis and in the chemical industry. New methodologies may also provide a new class of organoboronate compounds that cannot be obtained using conventional protocols. For example, the recent report that transition metals can catalyze the borylation of alkanes and arenes via C—H bond activation has already had a tremendous impact in organic synthesis (T. Ishiyama and N. Miyaura, J. Organomet. Chem. 2003, 680, 3).
Thus, there remains a continued need for an efficient synthesis of main group boryl compounds that requires mild reaction conditions and provides good yields.